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Autophagy plays an important role in mammalian oocyte maturation and early embryonic development and rapamycin is well known for inducing autophagy. Although previous studies have reported the effects of rapamycin on oocytes in vitro maturation (IVM) in different species, few studies have been reported on the role of rapamycin in yak oocytes IVM and embryonic development. Therefore, the objective of this study was to examine the effect of rapamycin treatment on yak oocytes IVM and early embryonic development. Specifically, immature yak oocytes during IVM or parthenogenetic (PA) embryos were treated with different rapamycin concentrations to select an optimal dose. Then evaluated its effect on maturation rates, cleavage, and blastocyst formation rates, mitochondrial membrane potential, ROS levels. Related genes and proteins expression in matured oocytes and blastocysts were also evaluated. The results show that 10 nM rapamycin treatment during IVM significantly improved oocyte maturation rates of oocytes and blastocyst formation rates. Treatment with 10 nM rapamycin reduced ROS level but increased mitochondrial membrane potential. Correspondingly, mRNA and protein expressions of LC3, Beclin-1, and Bcl-2 up-regulated while Bax down-regulated in matured yak COCs. When parthenogenetic embryos were treated with different rapamycin concentrations, 10 nM rapamycin treatment showed higher 8-cell and blastocyst formation rates. Also, CDX2, POU5F1, SOX2, and Nanog levels in blastocysts were upregulated. In summary, our findings demonstrate that rapamycin treatment improves oocytes maturation probably by increasing mitochondrial membrane potential, reducing ROS levels, and regulating the apoptosis in mature yak oocytes. Rapamycin treatment also improves embryonic developmental competence in the yak.

TAD (Topologically Associating Domain) reorganization occurs commonly in cell nucleus and contributes to gene activation and inhibition through separation or fusion of adjacent TADs. However, identification of functional genes impacted by TAD alteration and revealing of TAD- reorganization mechanism underlying gene transcription remain to be fully elucidated. Here, we firstly developed a novel approach termed Inter3D to specifically dig out genes regulated by TAD reorganization. By constructing the comprehensive TAD reorganization medicating epigenomic landscapes in tumor cells, we showed that TAD separation interrupted the intrachromosomal loop at MYL12B locus and abrogated its transcription, while TAD fusion generated the chromosomal interaction and triggered CYP27B1 activation. Our study provides a comprehensive insight into capture of TAD rearrangement-mediated gene loci and moves towards recognizing the functional role of TAD reorganization in gene transcription.

Targeting G protein-coupled receptors (GPCRs) through allosteric sites offers advantages over orthosteric sites in identifying drugs with increased selectivity and potentially reduced side effects. In this study, we developed a probe confined dynamic mapping protocol that allows the prediction of allosteric sites at both the GPCR extracellular and intracellular sides, as well as at the receptor–lipid interface. The applied harmonic wall potential enhanced sampling of probe molecules in a selected area of a GPCR while preventing membrane distortion in molecular dynamics simulations. The specific probes derived from GPCR allosteric ligand structures performed better in allosteric site mapping compared to commonly used cosolvents. The M2 muscarinic, β2 adrenergic, and P2Y1 purinergic receptors were selected for the protocol’s retrospective validation. The protocol was next validated prospectively to locate the binding site of [5-fluoro-4-(hydroxymethyl)-2-methoxyphenyl]-(4-fluoro-1H-indol-1-yl)methanone at the D2 dopamine receptor, and subsequent mutagenesis confirmed the prediction. The protocol provides fast and efficient prediction of key amino acid residues surrounding allosteric sites in membrane proteins and facilitates the structure-based design of allosteric modulators., Using specific probes from G protein-coupled receptor allosteric ligands, our probe confined dynamic mapping outperforms standard cosolvents and detects allosteric sites at extra-/intracellular sides and the lipid interface.

Allosteric modulators are called promising candidates in G protein-coupled receptor (GPCR) drug development by displaying subtype selectivity and more specific receptor modulation. Among the allosteric sites known to date, cavities at the receptor-lipid interface represent an uncharacteristic binding location that raises many questions about the ligand interactions and stability, the binding site structure, and how all of these are affected by lipid molecules. In this work, we analyze interactions in the allosteric sites of the PAR2, C5aR1, and GCGR receptors in three lipid compositions using molecular dynamics simulations. In addition, we performed quantum chemical calculations involving the symmetry-adapted perturbation theory (SAPT) and the natural population analysis to quantify the strength of intermolecular interactions. We show that besides classical hydrogen bonds, weak polar interactions such as O-HC, O-Br, and long-range electrostatics with the backbone amides contribute to the stability of allosteric modulators at the receptor-lipid interface. The allosteric cavities are detectable in various membrane compositions. The availability of polar atoms for interactions in such cavities can be assessed by water molecules from simulations. Although ligand-lipid interactions are weak, lipid tails play a role in ligand binding pose stability and the size of allosteric cavities. We discuss physicochemical aspects of ligand binding at the receptor-lipid interface and suggest a compound library enriched by weak donor groups for ligand search in such sites.

Gene expression and cell fate determination require precise and coordinated epigenetic regulation. The complex three-dimensional (3D) genome organization plays a critical role in transcription in myriad biological processes. A wide range of architectural features of the 3D genome, including chromatin loops, topologically associated domains (TADs), chromatin compartments, and phase separation, together regulate the chromatin state and transcriptional activity at multiple levels. With the help of 3D genome informatics, recent biochemistry and imaging approaches based on different strategies have revealed functional interactions among biomacromolecules, even at the single-cell level. Here, we review the occurrence, mechanistic basis, and functional implications of dynamic genome organization, and outline recent experimental and computational approaches for profiling multiscale genome architecture to provide robust tools for studying the 3D genome.

Two-dimensional (2D) heterostructures combine the advantageous features of different 2D materials and represent advanced electrode architectures for the development of efficient energy storage devices. However, common 2D heterostructures made by stacking different 2D sheets in van der Waals (vdW) contact impose obvious limitations in light of the energy storage performance. Here, we shed light on how heterointerface conditions exert a great influence on the electrochemical properties of the heterostructured electrode and provide an example to modulate the interface contact mode via sandwiching unique g-C3N4 mesh (m-g-C3N4). We find that such m-g-C3N4 bonded heterointerfaces can greatly increase the electrochemical activity, redox conversion kinetics and structural integrity of the constituent component (NiS2), manifesting excellent electrochemical performance with respect to vdW heterostructures. Experimental characterization along with theoretical simulations demonstrates that the synergistic effects of the mesh-bonded interfacial contact and plenty of in-between porous channels contribute to superior electrochemical performance. This study directs attention to elaborate interface engineering toward high-performance energy storage and paves the way for designing and manufacturing of advanced heterostructured electrodes for supercapacitors, batteries and other hybrid devices.

NiCoO2 (NCO) with a desirable redox activity, high lithium storage capacity and distinct rock-salt structure has gained increasing attention toward application in next-generation lithium ion batteries (LIBs) in comparison with other transition metal oxides (TMOs). However, the volumetric change and pulverization of the NCO electrode during the charge/discharge processes hugely limit its utilization in LIBs. In this study, we present a novel assembling protocol via integrating different structural configurations to address the general limitations of TMO anodes, which effectively improves the rate and cycling performance of the NCO anode. In addition, we provide an insightful understanding of the electrochemical behaviors of NCO through various ex situ characterization techniques and first-principles DFT calculations for the first time. This study reveals that the inherent rock-salt phase character of NCO could not only preserve 3D channels toward efficient ionic/electrical interdiffusion, but also retain high electrochemical reversibility during the long cycling process in comparison to the spinel NiCo2O4. Potential application of the NCO anode for LIBs has also been evaluated through assembling full cells. This study demonstrates the synergistic influences of the innate structure of NCO and elaborate composite architecture on the performance, paving the way for future design and manufacture of TMO anodes for practical applications.

High quality graphene (HQG) offers unconventional properties and is desirable for a variety of applications. However, facile solution processing (especially in water) and chemical bonding of functional components with the aim of achieving high-yield, green, and controllable synthesis of advanced graphene materials are of great concern. Herein, the surface chemistry of HQG is effectively tailored using a hydrophobic-driven assembly of cellulose macromolecules (CM) with various functionalities. In contrast to bulk or nanocellulose modifiers, surface engineering of HQG with densely carboxyl grafted CM renders stable aqueous graphene colloids via electrostatic repulsion. It also enables the use of efficient, low-cost, aqueous-phase synthetic techniques to create new HQG-based materials and devices. Highly exposed and reactive carboxyl and hydroxyl groups lead to in situ formation of evenly distributed Co3O4 nanoparticles on HQG sheets (HQG-COOH-Co3O4). We further demonstrate the potential application of two-dimensional HQG-COOH-Co3O4 heterostructures as supercapacitor electrodes with high power and energy density.

Lithium-sulfur (Li-S) batteries are one of the most promising candidates for meeting the emerging market demands for energy storage, and have the advantages including high energy density and low cost. However, the practical application of Li-S batteries is hindered by the lithium polysulfide (LiPS) shuttle, which induces low sulfur utilization and unsatisfactory capacity retention. To address this problem, recent studies have focused on improving the transformation of LiPS into insoluble Li2S2/Li2S through methods beyond physical or chemical adsorption. Nevertheless, the commonly used host materials have limited ability to simultaneously trap and propel redox transfer of LiPS. Herein, the bottom-up construction of new organic-inorganic hybrid frameworks for sulfur cathodes is proposed to fundamentally restrict LiPS dissolution and enhance their electrochemical transformation. The synergistic integration of organic cellulose networks and inorganic ZIF-derivatives caused highly efficient LiPS mediators to suppress the shuttle effect and retain electrode stability. The resulting RCE-Co3O4@G-S cathode materials delivered a stable capacity of 726.5 mA h g-1 at 0.2 C after 350 cycles, with a very low fading rate of 0.026% per cycle and a high coulombic efficiency of 98.9%.

Advances in the technology of wearable electronic devices have necessitated much research to meet their requirements, such as stretchability, sustainability, and maintenance-free functioning. In this study, we developed an ultrathin all-fiber triboelectric nanogenerator (TENG)-based electronic skin (TE-skin) with high stretchability, using electrospinning and spraying, whereby the silver nanowire (Ag NW) electrode layer is deposited between two electrospinning thermoplastic polyurethane (TPU) fibrous layers. Due to its extraordinary stretchability and prominent Ag NW conductive networks, the TE-skin exhibits a high sensitivity of 0.1539 kPa−1 in terms of pressure, superior mechanical property with a low-resistance electrode of 257.3 Ω at a strain of 150%, great deformation recovery ability, and exceptional working stability with no obvious fluctuation in electrical output before and after stretching. Based on the outstanding performances of the TE-skin, an intelligent electronic glove was fabricated to detect multifarious hand gestures. Moreover, the TE-skin has the potential to record human motion for real-time physiological signal monitoring, which provides promising applications in the fields of flexible robots, human-machine interaction, and multidimensional sports monitoring in next-generation electronics.

High-quality oocytes are a prerequisite for successful fertilization. Mammals feeding on aflatoxin-contaminated feed can cause reproductive toxicity, including follicular atresia, poor oocyte development and maturation, and aberrant epigenetic modifications of oocytes. In addition, the important role of ascorbic acid (AA) in reproductive biology has been confirmed, and AA is widely used as an antioxidant in cell culture. However, the toxic effects of aflatoxin B

Recent studies have reported that T-cell differentiation protein 2 (MAL2) is an important regulator in cancers. Here, we downloaded data from multiple databases to analyze MAL2 expression and function in pan-cancers, especially in ovarian cancer (OC). Gene Expression Profiling Interactive Analysis (GEPIA) databases was used to examine MAL2 expression in 13 types of cancer. Kaplan–Meier plotter database was used to analyze the overall survival rate of MAL2 in pan-cancers. The Catalog of Somatic Mutations in Cancer (COSMIC), cBioPortal, and UCSC databases were used to examine MAL2 mutation in human cancers. Metascape, STRING, and GeneMANIA websites were used to explore MAL2 function in OC. Furthermore, ggplot2 package and ROC package were performed to analyze hub gene expression and undertake receiver operating characteristic (ROC) analysis. Drug sensitivity of MAL2 in OC was examined by the GSCALite database. In order to verify the results from databases above, real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting were conducted to detect the expression of MAL2 in OC cells. CRISPR/Cas9 system was used to knockout the MAL2 gene in the OC cell lines HO8910 and OVCAR3, using specific guide RNA targeting the exons of MAL2. Then, we performed proliferation, colony formation, migration, and invasion assays to investigate the impact of MAL2 in OC cell lines in vivo and in vitro. Epithelial-mesenchymal transition (EMT)-associated biomarkers were significantly altered in vitro via western blotting and qRT-PCR. Taken together, we observed that MAL2 was remarkably dysregulated in multiple cancers and was related to patient overall survival (OS), mutation, and drug sensitivity. Furthermore, experimental results showed that MAL2 deletion negatively regulated the proliferation, migration, invasion, and EMT of OC, indicating that MAL2 is a novel oncogene that can activate EMT, significantly promote both the proliferation and migration of OC in vitro and in vivo, and provide new clues for treatment strategies.

With the development and maturity of inorganic nanomaterial technology, printed electronics which use traditional printing technology to make electronic devices or printed circuit board is gradually flourishing. Inkjet printing has attracted increasing attention in pixelated display as a mask-free, material-effective, flexibility and patterned deposition method to form functional patterns in optoelectronic and electronic devices. Quantum dots (QDs) have unique electronic and luminescent properties. Making full-color display based on quantum dot light emitting diodes (QLEDs) via inkjet printing is attractive in display industry owing to their compatibility with inkjet printing processes and their potential manufacturing advantages of large screen size and low cost. Although a large number of studies have shown that the resolution, film uniformity, and extended lifetimes of inkjet printed QDs display screens have all been improved, how to achieve high quality films and reduce the coffee ring effect through inkjet printing are the remain challenges for realizing QLEDs display. Thus it still requires the joint efforts of researchers in the whole field to realize the full printing of electroluminescent devices in industry.

Chromatin remodeling impacts the structural neighborhoods and regulates gene expression. However, the role of enhancer-guided chromatin remodeling in the gene regulation remains unclear. Here, using RNA-seq and ChIP-seq, we identified for the first time that neurotensin (NTS) serves as a key oncogene in uveal melanoma and that CTCF interacts with the upstream enhancer of NTS and orchestrates an 800 kb chromosomal loop between the promoter and enhancer. Intriguingly, this novel CTCF-guided chromatin loop was ubiquitous in a cohort of tumor patients. In addition, a disruption in this chromosomal interaction prevented the histone acetyltransferase EP300 from embedding in the promoter of NTS and resulted in NTS silencing. Most importantly, in vitro and in vivo experiments showed that the ability of tumor formation was significantly suppressed via deletion of the enhancer by CRISPR-Cas9. These studies delineate a novel onco-enhancer guided epigenetic mechanism and provide a promising therapeutic concept for disease therapy.

Bimetallic transition metal sulfides (TMSs) hold great promise as electrode materials for supercapacitive energy storage devices compared with their monometallic counterparts. However, it is still necessary to develop efficient synthetic protocols for favorable electrode architecture in order to further improve the electrochemical performance. This study presents a facile and controllable method to construct NiCo2S4 heterostructure based on electrochemically exfoliated graphene with good adhesion, which involves the growth of bimetallic MOF precursor and in-situ conversion into NiCo2S4 nanoparticles. This integrated architecture was found to be efficient for supercapacitive energy storage, as evident by the improved utilization of NiCo2S4 and excellent electrochemical performance including high capacity of 1802.5 F g−1 at 1 A g−1 and good rate capability (86.1% capacity retention at 10 A g−1). Additionally, N-doped mesoporous carbon spheres (NMCS) were synthesized by sacrificial template method and used as anode for practical application. Benefiting from good charge balance and compatibility, the assembled EEG@NiCo2S4//NMCS hybrid supercapacitor (HSC) exhibited outstanding energy density (30.4 Wh kg−1 at 800.0 W kg−1) and excellent cycling stability (80.1% capacitance retention after 9000 cycles).

A spectral clustering and Local Outlier Factor (LOF) based outlier mining algorithm, which is aiming to solve network intrusion detection problem, is proposed in this paper. First of all, the structure of similarity matrix method in spectral clustering is used for data preprocessing to find out the smaller similarity objects. During this process, the pruning of the outliers is completed, and a set of candidate outliers is obtained. Then, we calculate the local outlier factor of each data object in this set through LOF algorithm. And the final results of detection of outliers are acquired. The experimental results show that the proposed algorithm improves the accuracy of detecting outliers and the effectiveness of network intrusion detection.

Long shelf life is important for industrially packaged cooked chestnut kernel. This study aims to investigate the physicochemical and digestive properties of starch in cooked chestnut stored for varying periods of up to 12 months. Apparent amylose content decreases significantly during the initial storage period of 2 months and then increases gradually in the succeeding 10 months. During storage, the degree of gelatinization decreases, whereas the degree of retrogradation (DR) increases. The relative crystallinity of cooked chestnut starch increases during storage and shows a significant positive correlation with DR. The content of rapidly digestible starch (RDS) decreases significantly during shelf life. Starch retrogradation and relative crystallinity exhibit a significant negative correlation with RDS content, and the short‐range molecular order of starch is negatively correlated with the content of slowly digestible starch. The results indicate that the digestibility of cooked chestnut kernel decreases during storage because of an increase in the crystallinity of starch.